1. Field of the Invention
The present invention relates to the calibration of a mass spectroscope that uses an ion trap.
2. Description of Related Art
An ion trap mass spectroscope comprises a ring electrode having a hyperboloid of revolution of one sheet on the inner surface, and a pair of end-cap electrodes disposed opposite each other across the ring electrode and having a hyperboloid of revolution of two sheets on the inner surface. The space surrounded by the ring electrode and the end-cap electrodes forms an ion trapping area. When a predetermined high-frequency voltage is applied to the ring electrode and the pair of end-cap electrodes, a three-dimensional quadrupole electric field is formed in the ion trapping area, in which ions that are either internally generated or introduced from the outside can be trapped. The thus trapped ions move around in the space inside the electrodes at a frequency specific to their mass. In the ion trap apparatus, by applying an auxiliary AC voltage with a frequency corresponding to the mass of each ion to the end-cap electrodes while holding the trapped ions, a target ion can be caused to resonate and the amplitude of its motion can be increased, thereby allowing the ion to be discharged from the ion trap.
On the other hand, by applying a wideband noise that does not include the frequency components corresponding to the ion with a specific mass, end-cap electrode ions of other masses can be discharged from the electrodes while leaving the ion of the specific mass behind. Thereafter, if a weak resonance frequency voltage corresponding to the selected ion is applied, the motion energy of the ion can be increased while the selected ion is kept inside the ion trap. Consequently, the ion in the ion trap repeatedly collides with the helium gas or the like introduced in the ion trap, resulting in the dissociation of the ion (CID). This series of operations is referred to as MS/MS. By making a comparison between the original spectrum and the spectrum obtained after ionic dissociation, structural information about an organic compound can be obtained. Thus, MS/MS is a very important analysis technique in a variety of fields including pharmacy, biochemistry, and environment.
JP Patent Publication (Kokai) No. 7-14540 A (1995) (Patent Document 1) discloses an example of the conventional technique.
With regard to the target ion of a specific mass, it is necessary to accurately determine the value of a corresponding resonance frequency under specific conditions.
When a DC voltage U and a high-frequency voltage V cos Ωt are applied between the individual electrodes, a three-dimensional quadrupole electric field is formed in the space between those electrodes. The orbital stability of an ion trapped in this electric field is determined by the values a and q (Equations (1) and (2)) given by an internal radius r0 of the ring electrode, DC voltage U applied to the electrodes, amplitude V of the main high-frequency voltage and its angular frequency Ω, and the mass-to-charge ratio m/z of the ion.
                    a        =                                            8              ⁢              e              ⁢                                                          ⁢              U                                                      r                0                2                            ⁢                              Ω                2                                              ·                      z            m                                              (        1        )                                q        =                                            4              ⁢              e              ⁢                                                          ⁢              U                                                      r                0                2                            ⁢                              Ω                2                                              ·                      z            m                                              (        2        )            where z is the valence of the ion, m is mass, and e is elementary charge.
In conventional products, the DC voltage U is often not used, so that a=0. As a result, only Equation (2) becomes important. The angular frequency ω of the vibration specific to the ion of a particular mass can be calculated as follows.ω≈qΩ/2√{square root over (2)}  (3)
Thus, if r0 and Ω are fixed values, the vibration frequency of the ion of a specific mass in the ion trap can be uniquely determined by setting the amplitude (voltage) V of the high-frequency voltage at a certain value.
Actually, however, subtle deviations are produced in the actual ion and its resonance frequency from the calculated values due to factors such as subtle variations in the high-frequency voltage applied to the ring electrode and the pressure in the ion trap. Accordingly, the resonance frequency or the value of the main high-frequency voltage must be corrected periodically and for each apparatus. In other words, calibration must be performed, which generally involves the following operations.
At first, a standard sample of which the observed mass is known in advance is prepared, and the sample is introduced into an ion source at a fixed flow rate with use of a sample introducing device such as a liquid feed pump. The sample, which is fed continuously, is ionized in the ion source and introduced into a vacuum system via a sampling unit, before it is introduced into an ion trap via an ion transport unit. After the introduced ion has been trapped, a fixed main high-frequency voltage is applied to the ring electrode and, in this condition, an auxiliary AC voltage of a frequency that in calculation corresponds to the mass of the standard sample ion is applied to the end-cap electrodes, thereby causing the target ion to resonate and to be discharged from the ion trap. If there is any deviation, no resonance would occur at the calculated value setting, and the ion would not be discharged.
Therefore, the frequency of the main high-frequency voltage applied to the ring electrode or that of the auxiliary AC voltage applied to the end-cap electrodes is shifted slightly each time ions are fed to the detector, and a change in ion intensity is detected. When a condition under which resonance occurs is satisfied finally, ions are discharged from the ion trap and the ion intensity of the resultant spectrum decreases, thereby allowing the amount of difference between the calculated value and the actual value to be determined. Based on this result, the auxiliary AC frequency applied to the end-cap electrodes or the main high-frequency voltage applied to the ring electrode is corrected, thus completing the calibration process.
Patent Document 1 JP Patent Publication (Kokai) No. 7-14540 A (1995)
In the above calibration operation, the condition under which ions actually resonate and are discharged from the ion trap is determined by finely adjusting either the frequency of the auxiliary AC voltage applied to the end-cap electrodes that has a resonance frequency corresponding to the ion in the standard sample to be calibrated, or by finely adjusting the amplitude (voltage) of the main high-frequency voltage applied to the ring electrode. The ion intensity of the observed ion is recorded under varying conditions, until a resonance point is determined at which the lowest ion intensity is obtained. The standard sample is introduced into the ion source at a fixed flow rate during calibration such that a constant amount of ions can be supplied to the ion trap stably.
Actually, however, it is very difficult to keep supplying ions stably into the ion trap due to such troubles as deterioration of the performance of the pump that introduces the sample into the ion source, choked pipe, unstable operation of the ion source itself, and decrease in the efficiency of ionization caused by the contamination of the ion source, for example. In many cases, the ion intensity tends to change periodically or decrease with time.
It is therefore an object of the invention to provide a mass spectroscope capable of accurately and highly reliably determining the ion resonance condition, and a method of calibrating the spectroscope.